RETRACTED ARTICLE: Differential regulation of wild-type and mutant alpha-synuclein binding to synaptic membranes by cytosolic factors
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Post-publication record
- Nature
- Retraction
- Reason
- Duplication of/in Image;Unreliable Data;Upgrade/Update of Prior Notice(s);
- Date
- 6/3/2021 0:00
- Flagged by OpenAlex?
- Yes
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Abstract
BACKGROUND: Alpha-Synuclein (alpha-syn), a 140 amino acid protein associated with presynaptic membranes in brain, is a major constituent of Lewy bodies in Parkinson's disease (PD). Three missense mutations (A30P, A53T and E46K) in the alpha-syn gene are associated with rare autosomal dominant forms of familial PD. However, the regulation of alpha-syn's cellular localization in neurons and the effects of the PD-linked mutations are poorly understood. RESULTS: In the present study, we analysed the ability of cytosolic factors to regulate alpha-syn binding to synaptic membranes. We show that co-incubation with brain cytosol significantly increases the membrane binding of normal and PD-linked mutant alpha-syn. To characterize cytosolic factor(s) that modulate alpha-syn binding properties, we investigated the ability of proteins, lipids, ATP and calcium to modulate alpha-syn membrane interactions. We report that lipids and ATP are two of the principal cytosolic components that modulate Wt and A53T alpha-syn binding to the synaptic membrane. We further show that 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16:0 PAF) is one of the principal lipids found in complex with cytosolic proteins and is required to enhance alpha-syn interaction with synaptic membrane. In addition, the impaired membrane binding observed for A30P alpha-syn was significantly mitigated by the presence of protease-sensitive factors in brain cytosol. CONCLUSION: These findings suggest that endogenous brain cytosolic factors regulate Wt and mutant alpha-syn membrane binding, and could represent potential targets to influence alpha-syn solubility in brain.
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The record
- Venue
- BMC Neuroscience
- Topic
- Parkinson's Disease Mechanisms and Treatments
- Field
- Medicine
- Canadian institutions
- National Research Council CanadaInstitute for Biological SciencesUniversity of OttawaOccupational Cancer Research CentreUniversity of Toronto
- Funders
- Canadian Institutes of Health ResearchAlzheimer SocietyHeart and Stroke Foundation of Canada
- Keywords
- CytosolSynaptic vesicleBiochemistryMutantAlpha-synucleinBiologyCell biologyMembraneChemistryGeneEnzymeVesicleInternal medicine
- Has abstract in OpenAlex
- yes